Patients with Estrogen Receptor α-positive (ER+) Inflammatory Breast Cancer (IBC) are less responsive to endocrine therapy compared with ER+ non-IBC (nIBC) patients. The study of ER+ IBC samples ...might reveal biomarkers for endocrine resistant breast cancer.
Gene expression profiles of ER+ samples from 201 patients were explored for genes that discriminated between IBC and nIBC. Classifier genes were applied onto clinically annotated expression data from 947 patients with ER+ breast cancer and validated with RT-qPCR for 231 patients treated with first-line tamoxifen. Relationships with metastasis-free survival (MFS) and progression-free survival (PFS) following adjuvant and first-line endocrine treatment, respectively, were investigated using Cox regression analysis.
A metagene of six genes including the genes encoding for 4-aminobutyrate aminotransferase (ABAT) and Stanniocalcin-2 (STC2) were identified to distinguish 22 ER+ IBC from 43 ER+ nIBC patients and remained discriminatory in an independent series of 136 patients. The metagene and two genes were not prognostic in 517 (neo)adjuvant untreated lymph node-negative ER+ nIBC breast cancer patients. Only ABAT was related to outcome in 250 patients treated with adjuvant tamoxifen. Three independent series of in total 411 patients with advanced disease showed increased metagene scores and decreased expression of ABAT and STC2 to be correlated with poor first-line endocrine therapy outcome. The biomarkers remained predictive for first-line tamoxifen treatment outcome in multivariate analysis including traditional factors or published signatures. In an exploratory analysis, ABAT and STC2 protein expression levels had no relation with PFS after first-line tamoxifen.
This study utilized ER+ IBC to identify a metagene including ABAT and STC2 as predictive biomarkers for endocrine therapy resistance.
•ER+ inflammatory breast cancer (IBC) can be used as endocrine therapy resistance model.•Molecular characterization revealed ABAT and STC2 as ER+ IBC discriminatory genes.•ABAT and STC2 are novel biomarkers for tamoxifen resistance in advanced breast cancer.
The ALICE Collaboration reports three measurements in ultraperipheral proton-lead collisions at forward rapidity. The exclusive two-photon process γγ → μ+μ- and the exclusive photoproduction of J/ψ ...are studied. J/ψ photoproduction with proton dissociation is measured for the first time at a hadron collider. The cross section for the two-photon process of dimuons in the invariant mass range from 1 to 2.5 GeV/c2 agrees with leading-order quantum electrodynamics calculations. The exclusive and dissociative cross sections for J/ψ photoproductions are measured for photon-proton center-of-mass energies from 27 to 57 GeV. They are in good agreement with HERA results.
The pseudorapidity density of charged particles with minimum transverse momentum (pT) thresholds of 0.15, 0.5, 1, and 2 GeV/c is measured in pp collisions at the center of mass energies of $\sqrt{s}$ ...= 5.02 and 13 TeV with the ALICE detector. The study is carried out for inelastic collisions with at least one primary charged particle having a pseudorapidity (η) within ± 0.8 and pT larger than the corresponding threshold. In addition, measurements without pT-thresholds are performed for inelastic and nonsingle-diffractive events as well as for inelastic events with at least one charged particle having |η| < 1 in pp collisions at $\sqrt{s}$ = 5.02 TeV for the first time at the LHC. These measurements are compared to the pythia 6, pythia 8, and epos-lhc models. In general, the models describe the η dependence of particle production well. However, discrepancies are observed for the highest transverse momentum threshold (pT > 2 GeV/c), highlighting the importance of such measurements for tuning event generators. The new measurements agree within uncertainties with results from the ATLAS and CMS experiments obtained at $\sqrt{s}$ =13 TeV .
Measurement of the Λ hyperon lifetime Alizadehvandchali, N.; Alkin, A.; Alocco, G. ...
Physical review. D,
08/2023, Letnik:
108, Številka:
3
Journal Article
Recenzirano
Odprti dostop
A new, more precise measurement of the Λ hyperon lifetime is performed using a large data sample of Pb-Pb collisions at $\sqrt{s_{NN}}$=5.02 TeV with ALICE. The Λ and $\bar{Λ}$ hyperons are ...reconstructed at midrapidity using their two-body weak decay channel Λ→p+π- and $\bar{Λ}$→$\bar{p}$+π+. The measured value of the Λ lifetime is τΛ=261.07±0.37(stat.)±0.72(syst.) ps. The relative difference between the lifetime of Λ and $\bar{Λ}$, which represents an important test of CPT invariance in the strangeness sector, is also measured. The obtained value (τΛ-τ$\bar{Λ}$)/τΛ=0.0013±0.0028(stat.)±0.0021(syst.) is consistent with zero within the uncertainties. Both measurements of the Λ hyperon lifetime and of the relative difference between τΛ and τ$\bar{Λ}$ are in agreement with the corresponding world averages of the Particle Data Group and about a factor of three more precise.
A fully instrumented slice of the ATLAS detector was exposed to test beams from the SPS (Super Proton Synchrotron) at CERN in 2004. In this paper, the results of the measurements of the response of ...the barrel calorimeter to hadrons with energies in the range 20–350
GeV and beam impact points and angles corresponding to pseudo-rapidity values in the range 0.2–0.65 are reported. The results are compared to the predictions of a simulation program using the Geant 4 toolkit.
When considering nonoperative treatment in a patient with acute appendicitis, it is crucial to accurately rule out complicated appendicitis. The Atema score, also referred to as the Scoring System of ...Appendicitis Severity (SAS), has been designed to differentiate between uncomplicated and complicated appendicitis but has not been prospectively externally validated.
To externally validate the SAS and, in case of failure, to develop an improved SAS (2.0) for estimating the probability of complicated appendicitis.
This prospective study included adult patients who underwent operations for suspected acute appendicitis at 11 hospitals in the Netherlands between January 2020 and August 2021.
Appendicitis severity was predicted according to the SAS in 795 patients and its sensitivity and negative predictive value (NPV) for complicated appendicitis were calculated. Since the predefined targets of 95% for both were not met, the SAS 2.0 was developed using the same cohort. This clinical prediction model was developed with multivariable regression using clinical, biochemical, and imaging findings. The SAS 2.0 was externally validated in a temporal validation cohort consisting of 565 patients.
In total, 1360 patients were included, 463 of whom (34.5%) had complicated appendicitis. Validation of the SAS resulted in a sensitivity of 83.6% (95% CI, 78.8-87.6) and an NPV of 85.0% (95% CI, 80.6-88.8), meaning that the predefined targets were not achieved. Therefore, the SAS 2.0 was developed, internally validated (C statistic, 0.87; 95% CI, 0.84-0.89), and subsequently externally validated (C statistic, 0.86; 95% CI, 0.82-0.89). The SAS 2.0 was designed to calculate a patient's individual probability of having complicated appendicitis along with a 95% CI.
In this study, external validation of the SAS fell short in accurately distinguishing complicated from uncomplicated appendicitis. The newly developed and externally validated SAS 2.0 was able to assess an individual patient's probability of having complicated appendicitis with high accuracy in patients with acute appendicitis. Use of this patient-specific risk assessment tool can be helpful when considering and discussing nonoperative treatment of acute appendicitis with patients.
To determine the accuracy of final judgements of doctors at the emergency department (ED) and radiologists to differentiate between complicated and uncomplicated acute appendicitis, because these ...have different treatment options.
This prospective, multicenter study included adult patients with imaging-confirmed acute appendicitis, operated with intention to appendectomy. Both doctors at ED and radiologists assessed appendicitis severity as a final judgement of "uncomplicated" or "complicated" appendicitis. Doctors at ED integrated clinical, laboratory, and imaging findings. Radiologists relied solely on imaging findings. Outcomes were accuracy of these judgements for diagnosis of complicated appendicitis compared to the reference standard by an adjudication committee.
After imaging, 1070 patients with confirmed acute appendicitis were included. Doctors at ED accurately labelled 656 of 701 (93.6%) patients with true uncomplicated appendicitis as uncomplicated, and 163 of 369 (44.2%) patients with true complicated appendicitis were labelled as complicated. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for complicated appendicitis were 44.2%, 93.6%, and 78.4% and 76.1%, respectively. Comparable accuracy was found for the radiologist's assessment in 941 patients, with true positive rates of 92.2% (581 of 630 patients) for uncomplicated appendicitis and 46.6% (145 of 311 patients) for complicated appendicitis.
More than half of all patients with true complicated appendicitis is incorrectly classified as uncomplicated appendicitis according to the judgements of doctors at ED, integrating clinical, laboratory, and imaging results, and of radiologists assessing diagnostic imaging. These judgements are thereby not sufficiently reliable in ruling out complicated appendicitis.
Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke ...compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial.
NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy.
Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio HR 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity.
Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted.
Bayer and Janssen.
To assess the role of varicocele in male infertility.
Data analysis of a large population of couples who were systematically investigated for infertility.
Couples were recruited in 34 World Health ...Organization collaborating centers in 24 countries.
Nine thousand thirty-four men presenting as partner of infertile couples.
None.
Physical findings, semen characteristics, coincidental pathology, and spontaneous pregnancies.
Varicocele was found in 25.4% of men with abnormal semen, compared with 11.7% of men with normal semen. It was accompanied by decreased testicular volume, impaired sperm quality, and decline of Leydig cell secretion. Spontaneous pregnancies were as frequent in couples in whom the men did or did not have varicocele.
Varicocele is clearly associated with impairment of testicular function and infertility.
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